title: Continuation of mortality reduction after the end of randomized therapy in clinical trials of lipid-lowering therapy.
abstract: BACKGROUND
  Long-term follow-up of clinical trials with lipid-lowering medications has suggested a continuation of event reduction after study completion.
  
  
  OBJECTIVE
  To evaluate the persistence of the benefit of lipid-lowering therapy in decreasing mortality after the end of clinical trials, when all patients were advised to take the same open-label lipid-lowering therapy.
  
  
  METHODS
  Through searches of MEDLINE, the Cochrane Library, the Central Register of Controlled Trials, Web of Science, and ClinicalTrials.gov until June 2010 we identified randomized clinical trials of lipid-lowering agents with a second report describing results after the end of the trial.
  
  
  RESULTS
  Among the 459 trials reviewed, only 8 including 44,255 patients and 8144 deaths qualified for the meta-analysis. All-cause and cardiovascular mortality were lower in the active intervention group during the first phase (0.84, 95% confidence interval [CI] 0.76-0.93; P = .0006 and 0.72, 95% CI 0.63-0.82, P < .0001, respectively) when 71 ± 23% of the patients randomized to receive active therapy actually received it compared with 13 ± 5% of patients who received active therapy although they were randomized to placebo (P = .0001). The lower mortality among those initially randomized to active therapy persisted during the second phase (odds ratio 0.90, 95% CI 0.84-0.97, P = .0035, and 0.82 95% CI 0.73-0.93, P = .0014), when patients in both randomized groups received active therapy in the same proportions (5 ± 2% for both groups). Numerous sensitivity analyses support the conclusions of the paper.
  
  
  CONCLUSIONS
  The decrease in mortality with lipid-lowering therapy in clinical trials persists after discontinuation of randomized therapy when patients in the treatment and placebo groups receive active therapy.
authors.affiliation: Cardiology Division, Massachusetts General Hospital 55 Fruit St, GRB-800, Boston, MA 02114, USA. wkostis@partners.org
authors.forename: William J
authors.initials: WJ
authors.lastname: Kostis
authors.forename: Abel E
authors.initials: AE
authors.lastname: Moreyra
authors.forename: Jerry Q
authors.initials: JQ
authors.lastname: Cheng
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: Dobrzynski
authors.forename: John B
authors.initials: JB
authors.lastname: Kostis
mesh_terms: D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D009026:Mortality; D017594:Publication Bias; D016032:Randomized Controlled Trials as Topic; D013997:Time Factors
chemical_list: D000960:Hypolipidemic Agents